Hydrochloric Acid → Palonosetron hydrochloride

Participants

Reaction Conditions

Reaction Steps

The diastereomeric palonosetron (VIII) (16.5 g) obtained above was dissolved in 5% methanol in ethanol mixture (4.2 volumes). To it hydrochloric acid in ethanol was added and was heated to 70-75° C. Then N-bromosuccinimide (140 mg) was added at reflux. The solution was then cooled to 0 to 5° C. and 9.0 g of the precipitated crude palonosetron hydrochloride (I) were isolated by filtration. This obtained crude palonosetron hydrochloride (I) showing 95.90% of the desired (3aS,S) isomer, 3.10% of the undesired (3aR,S) isomer (Ia) and 0.04% of unreacted compound (IIa), when crystallized twice from ethanol-methanol mixture yielded 5.0 g of the title product (I) which was found to contain 99.66% of the titled compound (I), 0.29% of (3aR,S) isomer (Ia) and intermediate (IIa) below detection limit by HPLC analysis.

Provenance & Evidence